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Related Experiment Video

Updated: Jul 26, 2025

Preliminary Study on Acupuncture Combined with Grain-sized Moxibustion for Treating Rheumatoid Arthritis with Finger Joint Pain
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Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study.

Yang Gao1, Zheng-Rui Fan2, Fang-Yuan Shi3,4

  • 1School of Medical Technology, North Minzu University, Yinchuan, China.

Frontiers in Endocrinology
|June 16, 2023
PubMed
Summary

Hypothyroidism is causally linked to an increased risk of rheumatoid arthritis (RA). This study identified specific genetic variants, like rs4409785, contributing to this relationship, offering new insights into RA pathogenesis.

Keywords:
causal relationshiphypothyroidismrheumatoid arthritistwo-sample Mendelian randomizationvariants analysis

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Area of Science:

  • Genetics and Immunology
  • Endocrinology

Background:

  • The causal link between hypothyroidism and rheumatoid arthritis (RA) risk is debated, despite existing genome-wide association studies (GWAS).
  • This research aimed to rigorously test the hypothesis of a causal relationship between hypothyroidism and RA.

Approach:

  • Employed a two-sample Mendelian randomization (TSMR) analysis across European and Asian ancestries to assess causality.
  • Integrated functional annotations and variant prediction frameworks to identify and interpret instrumental variables (IVs).

Key Points:

  • Inverse variance weighted (IVW) analysis revealed a significant causal relationship between hypothyroidism and RA risk in European ancestry (OR = 1.96, p < 0.001).
  • Consistent results were observed across multiple MR methods (MR-Egger, weighted median) and validated in an independent Asian dataset.
  • The SNP rs4409785 was identified as a potential causal variant, influencing CTCF-cohesin binding and immune cell function.

Conclusions:

  • This study provides robust evidence for a significant causal association between hypothyroidism and an elevated risk of RA.
  • Identified potential causal genetic variants, advancing the understanding of RA's underlying mechanisms.